Drug already on the market could help treat MS and other neurological diseases

Multiple sclerosis, unless you suffer from nerve damage it is a pain you (thankfully) will never have to feel. In most cases, treating the brutal pain caused by this (and other neurological diseases) is the only help that can be offered to people. The pain is caused by damage to myelin, the fatty insulator that enables communication between nerve cells, which characterizes multiple sclerosis (MS) and other devastating neurological diseases.

The worst part of the whole thing is that the damage doesn’t come all at once. There is a “honeymoon” period during which some regeneration of myelin, called remyelination, does occur, unfortunately this ability to regenerate dissipates as the disease progresses and the person ages.

Now, researchers have discovered a way to keep that kind of remyelination going, using a drug that’s already on the market.

“We have identified a new drug target that promotes stem cell therapy for myelin-based disease, such as MS,” says lead author Fraser J. Sim, PhD.

“Our hypothesis is that in MS, the oligodendrocyte progenitor cells seem to get stuck,” Sim explains.

The approach the team took was to first characterize the molecular pathways that govern the differentiation of human oligodendrocyte progenitor cells, and then identify drug candidates that would promote differentiation and myelin production.

They found that when a muscarinic type 3 receptor on human oligodendrocyte progenitor cells was activated, differentiation was completely blocked.

“So we thought, if we had something that blocks instead of activates this receptor, could we boost differentiation?” asks Fraser.

To do that, the researchers turned to solifenacin, the anti-muscarinic drug for overactive bladder; the bladder muscle contains several muscarinic receptors.

“We were excited about this because solifenacin is an approved drug that’s already on the market,” says Sim.

To test whether the drug could boost myelin synthesis, the researchers transplanted human oligodendrocyte progenitor cells into mice that could not make myelin. The result was increased differentiation and myelin synthesis from the transplanted human cells.

But the researchers needed a functional endpoint, a way to know that the myelin being made was being translated into improved behavior or function.

So they teamed up with Richard J. Salvi, PhD, SUNY Distinguished Professor in the Department of Communicative Disorders and Sciences, and director of UB’s Center for Hearing and Deafness.

Together, they determined that an auditory brainstem response, which records brain wave activity in response to sounds, would be appropriate.

“It takes a certain amount of time for a signal to go from the ear to the front of the brain,” Sims explains

“So in the readout, you get waves that should have a certain time pattern. When there isn’t enough myelin, the signaling slows down. And if you add myelin, you should see the signals speed up.”

The tests showed improvement in the response to auditory signals in animals transplanted with the human oligodendrocyte progenitor cells treated with solifenacin.

“We have identified a way to improve human myelination,” says Sim.

The promising results have prompted the team to seek funding for a small human trial. It should also be noted that the study results are all preclinical and no human testing has been done yet. However, if the results are the same for humans, using it off label and even adding it to the list of prescribed drugs could come very quickly given it is already on the market. That is a big deal and possibly good news for anyone who suffers from a disease that causes demyelination.